All right. Welcome everybody. Thank you for joining at the back end of the corner of the conference. Really appreciate you found your way. I'm Christian Itin, the CEO of Autolus. Let me see. This is just our disclaimers. Please look at our SEC filings for the risk factors. We are at a very interesting point with the company.
We just launched our first product, which is called obe-cel . It's a CD19 CAR-T product that we have an approval for acute leukemia patients. These are the relapsed refractory population and in fact the adult population in that space. We had a very successful first year. We had $75 million in revenue in the first year of launch. We achieved market leadership very quickly.
We started the launch at the very beginning of last year. Within the second quarter, we reached market leadership. We also, as we went through the year, achieved approvals both in the U.K. and Europe. What was very important, by the end of the year, we also got through a positive NICE review.
That's the market access review in the U.K., which tends to be quite challenging for our line of products. We actually were deemed cost-efficient, and we're in routine commissioning, so we're not in the Cancer Drugs Fund, no need for additional data collection, and we launched the product in the U.K. at the very end of last year.
We're very lucky that actually a large part of our physicians, treating physicians of the U.S. are part of the ROCCA Consortium, and we're collecting actual clinical data, real-world data alongside the launch, and I'll briefly talk about that as we go through the presentation. I think it'll explain quite nicely for why the product resonates as much as it does and why it had a very strong initial uptake in the field.
We're also active in additional indications. We have a pivotal study ongoing pediatric patients, and we also have a pivotal study ongoing in lupus nephritis patients, which are patients that you would normally consider refractory to current therapies. They're post CD20 monoclonals and post calcineurin inhibitors. We have an exploratory study in progressive MS ongoing as well.
There's an opportunity to actually build on the exceptional profile that we have seen with the product in acute leukemia, a very challenging disease setting, into a much wider range of indications. With that, obviously this is an autologous CAR-T product, so manufacturing is a really critical part of the story. We actually set up our own manufacturing facility in the U.K., north of London, and you can see the facility on the right-hand side, the picture there. We've been able to actually supply at a very high success rate to the market.
We're above, substantially above a 90% manufacturing success rate with the product, which is very unusual for a first year of launch. You may remember many of the products in their first year had their issues and challenges.
We are exceptionally good at manufacturing and have been able to actually have very reliable and high quality delivery of the product, which is obviously particularly important with this particular patient population, which have very aggressive form of disease, very rapid progression of the disease. We have no capacity limitations.
What's important as we think about manufacturing, first half of last year, we really had to make sure we have a very robust, very stable delivery platform. We ran full steam through the first half of the year, then actually started to take in the learnings from that first half year, and we're now optimizing the manufacturing operation, and there's an really substantial opportunity to actually reduce the overall costs, ultimately the hours spent per product.
There's also a lot of opportunity to optimize pretty much every other aspect of the entire product supply chain. We're now driving towards really gross margin improvement, which is one of the key areas that will keep us busy for the next 24-36 months and will give us a very attractive trajectory with the company. We're also looking at advanced forms of automation.
In addition, this is now a semi-automated manufacturing process, and we're working on the next generation manufacturing platform. The important part is very robust, very reliable and cost efficient. Briefly, a few words to kinda the launch itself. In the U.S., we're currently present in approximately 70 centers across the country.
As you probably well know this type of therapy requires you to actually qualify each center and actually get that center onto your license, so it's quite an involved process to actually establish the delivery at a given center. Having 70 centers actually gives us a very broad reach across the population, and gives us access to the vast majority of patients in the U.S.
You can see the current distribution on the map. This is actually from our off public Autolus Assist website. You can see all the centers that are there. This is obviously for the patients when they try to actually locate a center close to where they are, and they can actually go on there. It's also publicly available, and you can see how we're moving forward.
We're expecting to go to 80+ centers during the course of this year, which gives us a very strong presence across the U.S. The guidance for this year is to $120 million-$135 million in net revenue. We're moving to positive gross margin in the year two of launch now, with that belief that we actually have a very strong opportunity to really drive market share, beyond, and this is CAR-T market share in this indication, in a significant way going forward.
I did mention the fact that most of our patients, about 60% of our patients were actually captured in the ROCCA database. This is a consortium of about 45 centers currently in the U.S. that collect all their clinical experience, real-world experience, from their acute leukemia patients into the database.
This has been particularly important because this is the physician's own experience with the product. What is obviously very important is obviously the safety profile, because that's the immediate experience that the physicians actually have with the product. As you can see, FELIX actually is the study that led to the approval of the product.
ROCCA is the database from this independent group of clinics across the U.S. collecting their actual experience in the commercial setting. We had zero patients experience high-grade CRS. This is a very tough population, as you may know. We also have only 3% of the patients that actually experienced high-grade ICANS, and only 17% actually had any form of ICANS. This is a remarkably good profile. If you compare to Blincyto, it's actually highly competitive, if not actually improved over the Blincyto profile.
Also compared to initial experience with CAR-T therapy in this space, that actually the real-world setting would indicate something in the range of 30% high-grade ICANS, as well as treatment-related mortality, which we had zero for our product. This is actually one of the key drivers why the product resonates as much, and obviously it comes together when you look at the overall response rate, which is above 90% in the real-world setting, or 78% in the FELIX study.
A remarkable profile and experience, and explains why the centers actually were as actually quick in adopting the product. Obviously, getting to market leadership with a fraction of the centers in the space actively delivering your product tells you a lot about the level of use within a given center that we actually achieved in there.
Very strong, I think, data, and I think very nicely corroborating in an independent way the actual experience and why the product performs the way it does. Now, when we think about expanding the opportunity, I did mention the fact that obviously we have pediatric and ALL and the lupus nephritis study that are actually ongoing as pivotal studies and the exploratory progressive MS study.
We also have, with our early-stage collaboration, programs that we have with UCL, we're working on a particular set of products. One particular area that we're following through the course of this year is a BCMA-targeting CAR-T together with CD19 component that we're testing or evaluating in light chain amyloidosis, and we expect to have probably early data by the end of this year.
When we think about how we sort of want to grow this franchise, the obicel franchise, from where the starting point, which is obviously in the relapsed refractory setting for adult patients with B-cell acute lymphoblastic leukemia, this is the approved indication. We have about 1,600 patients in the U.S. currently in that segment.
I think it's important to understand that Blincyto, before it moved into frontline setting, penetrated about 60% of that population. We expect our product with the profile to have that potential in that setting as well. The pediatric patients, obviously, we have made huge progress for the treatment of pediatric ALL patients. A lot of the kids get cured priced on the high-dose chemotherapy regimens upfront and also Blincyto consolidation added to that.
There's still about somewhere to 400 patients that we think we can add here in the U.S. That actually allows us to sort of expand the utility in a very high medical need setting. Lupus nephritis obviously is a fraction of the overall lupus market, and we're focusing on the most severe forms of that disease, which is why this is substantially smaller than what you would normally refer to with lupus, but very sizable.
Obviously a step change in terms of the patient volume and also a very, very high medical need, obviously progressive MS, where we are in an exploratory study. We believe we have an opportunity to really take that remarkable profile that we have with obe-cel.
Remember, this is built on a very differentiated mechanism of action, which is different from the other CAR-Ts in the space, which gives us actually the profile that we're seeing. There's a very different way of how we're engaging the target cells. It's a much more physiological way that gives us actually higher potency, but at the same time also reduces toxicity.
With that, we're looking quickly at the pediatric path that we're on. We have just presented the phase I experience from the pivotal study, which is a phase I, II study at ASH at the end of last year. We're now actually have moved into the phase II portion of the study, which is an additional 30 patients.
This is a single-arm study, includes actually patients that are high-risk frontline patients that are currently actually not included in any label for CAR-T therapy in this setting. Now, when we look at the data, obviously, again, a good safety profile. We had 1 patient have both a high-grade CRS and high-grade ICANS. Overall, the data we have, very, very similar to what we're observing in the adult population.
These are obviously patients that have pretty substantial tumor burden as well. This is just a swimmer's plot, you can see these patients do remarkably well. With the exception of 1 patient, everybody actually responded to therapy and got to a complete remission. You see very nice progression in terms of time progression for these patients. We're very hopeful that these patients will have very nice outcomes.
This is obviously includes very difficult to treat patients in this particular setting. When we look at the rationale for why we're obviously moving into the autoimmune space, it has a lot to do with the profile that we have with the product. What we can do is we can basically take out efficiently the CD19 positive B-cell compartment. Why does that matter?
It matters because that is obviously where the memory sits of the autoimmune disease of, that actually drive autoreactive antibodies, but it also includes the plasmablasts. Plasmablasts are early stages of plasma cells, and what we have learned through the work that was done at Georg Schett's team in Erlangen is that remarkably, it's those cells that seem to be producing most, if not all, of the autoreactive antibodies.
This is a very unusual finding from a biology perspective, something that was not known until actually that particular test became available, and you could actually get to a very deep reset of the CD19 B-cell compartment. We obviously have the only product from a CAR-T perspective in this space that actually has an approval anywhere.
We have obviously more than 500 patients' safety data with the product, and we're using the same product that we are using in oncology, we're using in autoimmune disease, so that data matters. That BLA matters because it's transferable and supportive of the autoimmune indications. At the same time, one of the key elements when you think about risk and investment and volumes that you need is obviously the ability to actually be able to supply. Having an established commercial manufacturing infrastructure is critical.
We have that infrastructure. We established it. We've showed and proven commercially that we can deliver with high reliability. That obviously is a huge asset and also reduces the overall amount of capital needed to get into these indications because obviously every company that's currently with a new product underway, they need to establish that.
Or adjust it if they had been in the CAR-T space, but obviously modified their programs, so that they become, from an FDA perspective, new programs. This is a quick view on the initial phase 1 experience. This is the CAROUSEL study. We included here patients that had, these are SLE patients with severe forms of disease. They all had to have organ involvement. They had to have an active, ongoing disease.
When we look at the median SLEDAI score in this population was 17. This is the highest of any of the studies that actually reported to date. We have overall a very good safety profile. We had half of the patients experience a grade one CRS. That's a fever of about 38 degrees. That's actually obviously manageable with paracetamol.
This is not obviously anything that normally you would consider CRS from an adverse event perspective. No, none of the patients experience an ICANS of any kind. It's a very good safety profile in a very difficult population. Now, when we look at the DORIS response, what the DORIS response does, it does take basically composite outcome coming from the SLEDAI scores, and I'll share those with you as well.
In addition, requires actually that the corticosteroids goes down to physiological levels of 5 milligrams pred. That is obviously needed because these patients actually have been for years on steroid treatment, so you can't completely obliterate or stop giving steroids, but you go down to physiological levels, and at that point, you actually achieve a DORIS response.
What you can see is that five of those six patients achieved the DORIS response, which is a response which is very encouraging. Three of the six also had a complete renal response. That's a filtration based on the filtration performance of the kidney, a direct biochemical measure of the function of the kidney in these patients. This is a view on the SLEDAI-2K scores. This is a composite score.
What's very typical for these patients is that they do not only have SLE, but they actually have several manifestations of autoimmune disease. Many of these patients have mucosal ulcers, alopecia, vasculitis, they may actually have arthritis. They have obviously, with the exception of one, all of these patients had renal involvement. They tend to have leukopenia, low complement levels because the autoreactive antibodies are consuming the complement.
What you can see is that over time, although these patients started all in a very difficult spot, over time, the scores actually improve substantially. What you see in a number of the patients is a level of DNA binding. This is actually a binary result, which is frankly, you're above detection level or below. If you're above, it actually gets an automatic score.
When you look at the actual progression of the double-strand DNA antibodies, you can actually see a massive reduction in these patients in terms of the actual levels. For many of these patients, you will see continued level without any evidence of autoimmune disease.
A remarkable outcome, obviously a lot of improvement that these patients do see for many of these patients very quickly. Most of the experienceable components of lupus or of SLE tend to be gone within about one to maximally three months. Quite remarkable. You can see, you know, we had, you know, SLEDAI scores of 28 at the top end of the range. This is absolutely horrific.
The path we're taking is we're obviously taking now this program into a pool of lupus nephritis patients that have gone through B-cell depleting antibodies and also have gone through calcineurin inhibitors. At this point, you have no further approved therapy available in, at that stage of the disease. We're now taking these patients with active ongoing disease into a pivotal study. It's a single arm study, 30 patients, for full approval.
That's designed for a full approval. Obviously critical here is the definition of the patients. This study is called the LUMINOUS study, which is designed for initial approval and from there on, we're planning to then actually go to an expanded indication with a randomized controlled study in less severe patients from there on forward.
Looking at the market, obviously the overall SLE market in the U.S. is very large. It's, you know, close to 350,000 patients across the U.S. and across all the various stages of disease. If you actually look at the lupus nephritis population, it goes down to 110. If you look at the severe population, it's between 70-90. The ones that are refractory to standard of care are about 25,000-35,000 patients. It's a sizable population. It's about three times, probably 10 times the population that we have in acute leukemia, so this is very meaningful.
We believe this is going to give us a very attractive transition into that state also where we and also in an indication where we have a very strong health economic argument that actually supports pricing as well for this indication. MS, kind of a different space. Obviously the challenge that we have with MS, that's it's obviously an autoimmune disease, but it's an autoimmune disease in the brain.
One of the key challenges that we have with all the systemic therapies, typically CD20 monoclonals and other forms of small molecule like S1P inhibitors, these molecules tend not to actually cross the blood-brain barrier. One of the fundamental opportunities you have with a CAR T-cell therapy is that the T-cells very efficiently cross the blood-brain barrier, and they're very active in the brain.
Why do we know that? We know it because we've actually a lot of the patients that we have in acute leukemia have CNS involvement. They have disease. They have leukemia cells in the brain. We can show that those leukemia cells are being taken out by our product, and we can also measure the presence of our product in the CSF, in the spinal fluid. We know the cells do cross very effectively, and they're very active. In addition, we've also run a study in primary CNS lymphoma.
That is where the lymphoma actually is formed in the brain and actually grows in the brain, and we could show very high level of activity with obicell in those patients as well. We do know the product goes to the place where we're particularly concerned about and where other therapeutic options don't get there.
The disease setting we're going after are patients that have progressive MS. Progression is defined here as patients that have been at least for six months on CD20 monoclonal and S1P inhibitors and continue to deteriorate. It has to be actually continuous decline, the patient have to be in continuous decline.
We also wanna make sure they're not so far down the disease score that there's an opportunity to still stabilize them and hopefully, you know, get them to a sort of a place where they can stop, we can stop progression. What we're looking at is a so-called EDSS score, which is the clinical score for these patients, and we're gonna include patients that are between 3 and 6.5 in that score. That's how what we include.
These patients have an enormous medical need because, and a high awareness around their disease, because they know they're gradually getting worse, and they know none of the therapies really stops that progression. Most of the patients are female, and most of them are actually in childbearing age. They're typically in their 20s, early 30s.
They're acutely aware of the situation, and there's a very, very high demand actually for patients to have access. I've never seen the dynamic that we've seen in this study with any other clinical study, not even in acute leukemia, where patients know they have a high probability of dying in a short period of time. The motivation of these patients to get on study has been stunning. We're running this study.
We expect to have early data end of this year, early next year, and then obviously more mature data during the course of next year. Obviously we'll need to see where we end up, but I think if this turns out to be positive, that could also be a significant step change for the program because that's a large indication, very high medical need, and likely an ability to enroll whatever the registration trial will become in a very fast way.
Obviously the opportunity is sizable because the whole segment of progressive MS is about 300,000 patients in the U.S. This is a very large market with a very high medical need, a very well-informed patient population, and I think an ability, if you have a good outcome, to really translate in a very attractive way.
The upcoming milestones are kinda long-term follow-up from the initial SLE experience, which also includes adolescent patients, which I haven't talked about. But we included patients from 12 years and older. A lot of the starting point for autoimmune disease, in many of these patients are actually in their teens.
It is important to include those patients. We expect initial data from the MS study, that's the BOBCAT study. We have initial data from the amyloidosis study with AUTO8. Obviously expect to have our pivotal study in pediatrics enrolled early 2027, obviously from there on, obviously are getting, looking for data towards the end of 2027 for the pediatric study.
With regards to the lupus study, we'll need to have a longer follow-up, in terms of the clinical endpoint, and we expect the study on the lupus results to sort of become available during the course of 2028. That's kind of where we are. With that, I will just kind of summarize. We're at a very strong position.
We have had a very strong launch. We're have a very good start into the second year of the launch. We're expanding into the U.K. now. We're negotiating on the European side for market access. We're currently not guiding to any revenue in Europe. We'll need to see how that goes.
We're obviously are in a process of optimizing our systems and with that really driving the gross margin, and driving for positive gross margins around the manufacturing as well as the commercial model, and expanding the opportunity into additional indications and with that really driving the upside for the business around our lead program. That's it for today. Happy to take questions. All right. On that note, I'll be gonna wish you a fantastic day and hopefully no snow in the afternoon. I know. We gotta have hope.